Xiaowei Lu, PhD, Harrison Distinguished Teaching Professor of Cell Biology, has been awarded a five-year $2.9 million grant from the NIH National Institute on Deafness and Other Communication Disorders to research microtubule-mediated mechanisms underlying hair cell development and deafness. This NIH award funds years 11 to 15 of Dr. Lu’s research on molecular and genetic mechanisms of hearing and deafness.
Sensory hair cells in the cochlea convert sound vibrations into electric signals. This mechanoelectrical transduction process is critically dependent on the actin-based stereociliary hair bundle that projects from the hair cell apical surface.
“Defects in hair bundle formation and maintenance due to genetic and environmental factors are a leading cause for sensorineural hearing loss,” said Dr. Lu.
While hair bundle formation requires many actin regulators, Dr. Lu and other researchers have shown that hair cell apical microtubules play important roles in establishing the proper structure of the hair bundle. However, the underlying processes mediated by hair cell microtubules that control hair bundle morphogenesis remain poorly understood.
Dr. Lu’s lab recently discovered a novel deafness gene that encodes a scaffold protein localized to the microtubule organizing center of the hair cell.
“We found when this gene is missing, mice are deaf with severe defects in hair cell microtubule organization and hair bundle structure, revealing an essential role of this gene in coupling microtubule organization with hair bundle formation,” said Dr. Lu.
To investigate this, the Lu lab will identify key effectors recruited by this scaffold protein and determine their functions in normal hearing using a multidisciplinary approach.
A long-term objective of this work is to gain a mechanistic understanding of developmental programs that govern hair bundle morphogenesis and use the new insights to inform future molecular therapies for hair bundle repair and hearing restoration.
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